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Stable suspensions of NiO and/or Mn 3 O 4 nanoparticles with a mean diameter of 16.7 ± 8.2 nm and 18.4 ± 5.4 nm, respectively, prepared by laser ablation of 99.99% pure metals in de-ionized water were repeatedly injected IP to rats at a dose of 0.50 mg or 0.25 mg 3 times a week up to 18 injections, either separately or in different combinations. Many functional indices as well as histological features of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The accumulation of Ni and Mn in these organs was measured with the help of AES and EPR methods. Both metallic nanoparticles proved adversely bio-active, but those of Mn 3 O 4 were found to be more noxious in most of the non-specific toxicity manifestations. Moreover, they induced a more marked damaging effect in the neurons of the caudate nucleus and hippocampus which may be considered an experimental correlate of manganese-induced parkinsonism. Mathematical analysis based on the Response Surface Methodology (RSM) revealed a diversity of combined toxicity types depending not only on particular effects these types are assessed for but on their level as well. The prognostic power of the RSM model proved satisfactory. [ABSTRACT FROM AUTHOR]

Highlights: [•] Effects of repeated i.p. injections of Cd, Pb or Cd+Pb in doses isoeffective in relation to LD50 were studied on rats. [•] Analysis of results with either ANOVA or the Theory of Experimental Design gave similar assessments of combined toxicity. [•] Thus paradigms of effect or dose additivity can be regarded as different ways of modelling the basically same phenomenon. [•] The type of combined toxicity depends on which effect is considered as well as on the dose levels and their ratio. [Copyright &y& Elsevier]

This investigation continues our study of the effects of Pb-Cd poisoning on the heart, extending the enquiry from isometric to auxotonic contractions, thereby examining the effect on the ability of myocardial tissues to perform mechanical work. Different shifts were revealed in myocardial force-velocity relations following subchronic exposure of rats to lead acetate and cadmium chloride acting separately, in combination, or in combination with a bioprotective complex (BPC). The experiments were conducted on isolated preparations of trabecules and papillary muscles of the right ventricle in physiological loading conditions and on isolated heart muscle contractile proteins examined by the in vitro motility assay. The results of the latter correlate with the shifts in the ratio of cardiac myosin isoforms. The amount of work performed by the myocardium was calculated on the basis of the tension-shortening loop area and was found to be similar in the preparations from all experimental groups. This fact presumably reflects adaptive capacity of the myocardial function even when contractility is damaged due to the metallic intoxication of a moderate severity. Some characteristics of rat myocardium altered by the impact of lead-cadmium intoxication became fully or partly normalized if intoxication developed against background administration of a bioprotective complex (BPC). Together with previously reported results obtained in the isometric mode of contractility, all these results strengthen the scientific foundations of risk assessment and risk management projects in the occupational and environmental conditions characterized by human exposure to lead and/or cadmium. • The experiments were conducted on preparations of trabecules and papillary muscles and on myocardium proteins. • Force-velocity and the in vitro motility assay data were changed following subchronic exposure of rats to Pb and Cd. • These shifts become fully or partly normalized against background administration of the proposed bioprotective complex. [ABSTRACT FROM AUTHOR]

Outbred male rats were repeatedly injected intraperitoneally two-level sub-lethal doses of lead acetate and/or cadmium chloride solutions 3 times a week during 6 weeks. The animals developed explicit, even if moderate, subchronic intoxication characterized by a large number of indices, both common to both metals (including increased DNA fragmentation coefficient) and lead-specific. Special attention was paid to hemodynamic and electrocardiographic effects. The combined action of lead and cadmium was modeled with the help of the Response Surface Methodology to obtain additional support for the previously substantiated postulates of combined toxicity's typological ambiguity. This is dependent on which particular effect comes under consideration, on its level, and on the acting dose ratio. For one and the same toxic combination, the type of combined toxic action can vary from synergistic to contra-directional. In particular, the actions of lead and cadmium on blood pressure were found to be opposite in direction. Furthermore, it is shown once again that the systemic toxic effects of a metal combination, its in vivo genotoxicity included, can be more or less attenuated by background administration of a theoretically justified composition of biologically active agents. • Rats repeatedly injected IP with Pb acetate and/or Cd chloride developed outcomes either common to Cd and Pb or Pb-specific. • For the first time, hemodynamic and electrocardiographic effects of this toxic combination was studied. • Causal association of many features with Cd or Pb impact was confirmed by their correlation with blood metal level. • For one and the same toxic combination, the type of combined toxicity can vary from synergistic to contra-directional. • Many toxic effects of the combination, genotoxicity included, were attenuated by background administration of bioprotectors. [ABSTRACT FROM AUTHOR]